Subclinical involvement of eye movements detected by video-based eye tracking in myasthenia gravis.

BACKGRO UND: Ocular abnormalities in myasthenia gravis (MG) are characterized by severely limited movements and rapid saccades. Data about eye motility of MG patients whose ocular movements are apparently normal are lacking. Our study assessed the eye movement parameters in MG patients without clinical eye motility dysfunctions and investigated the effects of neostigmine administration on the eye motility in these patients. MATERIALS: In this longitudinal study, we screened all patients diagnosed with MG referring to the Neurologic Clinic of the University of Catania between October 1, 2019, and June 30, 2021. Ten age- and sex-matched healthy controls were enrolled. Patients underwent eye movement recording using the EyeLink1000 Plus® eye tracker at baseline and after 90 min from the intramuscular administration of neostigmine (0.5 mg). RESULTS: A total of 14 MG patients with no clinical signs of ocular motor dysfunction (64.3% men, with a mean age of 50.4 ± 14.4 years) were enrolled. At baseline, saccades in MG patients showed slower velocities and longer latencies compared to controls. Moreover, the fatigue test induced a reduction in saccadic velocity and an increase in latencies. After neostigmine administration, the ocular motility analysis showed shorter saccadic latencies and a significant improvement of velocities. CONCLUSIONS: Eye motility is impaired even in MG patients with no clinical evidence of ocular movement disturbance. Video-based eye tracking may detect subclinical involvement of eye movements in patients with MG.

Pure sensitive chronic inflammatory axonal polyneuropathy following Pfizer COVID-19 vaccine.

BACKGROUND: During the worldwide mass vaccination campaign against SARS-CoV-2, multiple side effects have been observed. We described the case of a patient who developed pure sensitive chronic inflammatory axonal polyneuropathy (CIAP) in a close temporal relationship with the administration of the BNT162b2 (Pfizer®) vaccine. CASE REPORT: An 82-year-old woman developed lower limb sensory loss and "pricking" associated with marked gait imbalance after she had received her second dose of Pfizer-BioNTech COVID-19 vaccine. At the electroneurographic examination, the motor nerves conduction study was normal. Median, ulnar, and sural nerves sensory compound nerve action potential (CNAP) were bilaterally absent. Somatosensory evoked potentials (SSEPs) were not recordable. Spine MRI demonstrated roots enhancement from C3 to Th2 and diffuse enhancement of cauda equina nerve roots. She was treated with IV methylprednisolone whit benefit. A follow-up visit was made 4 months after the disease onset; a diagnosis of pure sensitive CIAP has been made. DISCUSSION: To the best of our knowledge, this is the first description of CIAP occurring in a close temporal relationship with the administration of Pfizer-BioNTech COVID-19 vaccine.

An update on idiopathic intracranial hypertension in adults: a look at pathophysiology, diagnostic approach and management.

Idiopathic intracranial hypertension is a neurological syndrome determined by a rise in intracranial pressure without a detectable cause. Course and prognosis may be changeable, requiring a multidisciplinary approach for its diagnosis and management. Although its precise pathogenesis is still unknown, many studies have been carried out to define the possible causal and associated factors, such as retinoids, steroid hormones, body mass index and recent weight gains, cytokines and adipokines levels. The clinical presentation can be variable including chronic headache, disturbance of vision, diplopia and tinnitus. Even if papilloedema is considered the most specific sign, it could not be observed in more than 5% of patients during the evaluation of the fundus oculi. Neuroradiological signs acquire greater importance in patients who do not present papilloedema and may suggest the diagnosis of idiopathic intracranial hypertension. Other assessments can be useful in the diagnostic process, such as optical coherence tomography, visual evoked potentials, ocular ultrasonography and fundus fluorescein angiography and autofluorescence. Nonetheless, cerebrospinal fluid pressure measurement is required to establish a definite diagnosis. Management may be different, since surgical procedures or lumbar punctures are often required when symptoms develop rapidly leading to a loss of visual function. Apart from these cases, patients can be treated with a pharmacological approach and low-calorie diet, but they also need to be monitored over time since relapses years later are not uncommon.

Clinical and CN-SFEMG evaluation of neostigmine test in myasthenia gravis.

Neostigmine test (NT) is a pharmacological test, demonstrating a clinical improvement in patients affected by myasthenia gravis (MG). We aim to compare clinical evaluation and neurophysiological recordings by concentric-needle single-fiber electromyography (CN-SFEMG) in response to acute administration of neostigmine in ocular and generalized MG patients. Twenty-three MG patients (10 with ocular MG and 13 with generalized MG) were evaluated before and after 90 min neostigmine 0.5-mg administration. Clinical responsiveness was assessed by MG composite (MGC) scale. Neurophysiological evaluation by CN-SFEMG considered analysis of mean value of consecutive differences (MCD), single-pair jitter, and blocks. MGC scores significantly improved after NT in generalized MG patients (MGC 11.1 ± 7.6 vs 9.1 ± 6.7, p = 0.02), whereas the improvement was not significant in the ocular group. CN-SFEMG recordings significantly improved after NT in generalized MG patients (MCD 58.9 ± 18.8 vs 45.9 ± 23.2 µs, p = 0.003; single-pair jitter 49.8 ± 26.9 vs 24.1 ± 26.7%, p = 0.0001; blocks 6.2 ± 9.5 vs 2.6 ± 7.4%, p = 0.03) as well as in ocular MG patients (MCD 50.8 ± 22.7 vs 40.1 ± 22.9 µs, p = 0.01; single-pair jitter 35.9 ± 23.7 vs 20.0 ± 25.1%, p = 0.001). CN-SFEMG is a reliable tool to evaluate responsiveness to acute administration of neostigmine in MG. Moreover, neurophysiological modifications to NT could show subclinical improvement in ocular MG better than that of the clinical scale.

Vascular parkinsonism or idiopathic NPH? New insights from CSF pressure analysis.

Differential diagnosis between vascular parkinsonism (VP) and idiopathic normal pressure hydrocephalus (iNPH) is particularly challenging due to similar clinical and neuroradiological features. The objective of this study is to differentiate VP with radiological evidence of ventricular enlargement (REVE) from iNPH on the basis of cerebrospinal fluid (CSF) hydrodynamics. CSF pressure components were investigated in patients with a clinical diagnosis of VP and REVE. Data of eight patients (seven men; age 76 ± 3.9 years; disease duration 26.5 ± 15.6 months) were evaluated. CSF opening pressure values were normal in all patients. Also, mean CSF pressure values during short-term monitoring were normal, except in one patient. Four out of the eight patients had raised values of pulse wave amplitude (PWA) during the opening phase (mean ± SD 57.1 ± 19.9 mmH2O), meanwhile during short-term monitoring, seven out of the eight patients showed raised values of mean PWA (76.8 ± 23 mmH2O). We found that most of patients with clinical characteristics of VP and REVE showed elevated PWA during the short-term monitoring of CSF pressure as observed in iNPH patients. Patients clinically identified as VP may be part of the clinical spectrum of iNPH.

Migraine causes retinal and choroidal structural changes: evaluation with ocular coherence tomography.

Few studies have evaluated whether the retina is involved in migraine through the evaluation of retinal nerve fiber layer (RNFL) examined with ocular coherence tomography (OCT) with conflicting results. Aim of this case-control study is to evaluate the retina and the choroid in migraine. Patients having migraine with aura (MwA) or without aura (MoA) and chronic migraine (CM) were evaluated. Age- and sex-matched normal subjects were selected as healthy controls (HC). Patients and HC were examined with OCT. RNFL, ganglion cell layer (GCL), foveal thickness (FT), choroidal thickness (CT) and total macular volume (TMV) were calculated for right eyes (RE) and left eyes (LE). Seventy-seven patients (62 women; 80.5%), 21 MoA, 12 MwA, 44 CM and 42 HC were enrolled in the study. Patients compared to HC had a significant reduction of RNFL (RE: 91.2 ± 9.2 vs 99.3 ± 7.5 µm; p < 0.001. LE: 93.3 ± 8.7 vs 100.2 ± 6.5 µm; p < 0.001). GCL (RE: 80.6 ± 6.4 vs 86.9 ± 2.1 µm; p < 0.0001. LE: 81.5 ± 5.7 vs 87.1 ± 2.6 µm; p < 0.0001) and CT (RE: 286.4 ± 31.4 vs 333.2 ± 3.1 µm; p < 0.0001. LE: 287.2 ± 31.6 vs 334.5 ± 4.1 µm; p < 0.0001) were thinner in patients compared to HC. Moreover, CM showed reduction of RNFL and of GCL compared to the other migraineurs. Finally, we found a significant inverse correlation between RNFL thickness and total number of headache attacks per months. Our data suggest the involvement of retina and choroid in migraineurs, especially in the CM group. Although migraine is an episodic and recurrent disease, its chronic nature might cause permanent structural abnormalities involving not only the brain, but also the retina.

Effect of botulinum toxin treatment on quality of life in patients with isolated lingual dystonia and oromandibular dystonia affecting the tongue.

The purpose of this study was to investigate the impact of botulinum toxin (BoNT) treatment on the quality of life (QoL) for patients with prominent lingual dystonia (LD) using a disease-specific questionnaire, the oromandibular dystonia questionnaire-25 (OMDQ-25). This is a prospective, observational study of a cohort of 30 patients treated with BoNT injections for LD, with or without concurrent jaw dystonia. Primary efficacy outcome was the absolute difference between total OMDQ-25 baseline score and total OMDQ-25 scores 4 and 8 weeks after the treatment. Safety outcome was the occurrence of adverse effects. The mean total OMDQ-25 baseline score was 46.8 ± 17.8. After BoNT treatment, there was a significant reduction in the mean total OMDQ-25 score at 4 weeks (38.2 ± 17.6; p = 0.004), as well as at 8 weeks (39.6 ± 18.1; p = 0.008). At the multiple regression analysis, a jaw deviation pattern (JDD) and high questionnaire baseline total score were detected as predictors of a better outcome, whilst associated jaw tremor was a predictor of poor outcome. In patients with JDD, jaw-opening muscles were more frequently injected and genioglossus less frequently than in patients without JDD. No major adverse events were detected. A consistent and measurable improvement in QoL, with good safety and tolerability, can be achieved in patients with prominent LD by injecting BoNT into genioglossus and/or other muscles of the oromandibular region.

Clinical and radiological features of extra-pulmonary sarcoidosis: a pictorial essay.

UNLABELLED: The aim of this manuscript is to describe radiological findings of extra-pulmonary sarcoidosis. Sarcoidosis is an immune-mediated systemic disease of unknown origin, characterized by non-caseating epitheliod granulomas. Ninety percent of patients show granulomas located in the lungs or in the related lymph nodes. However, lesions can affect any organ. Typical imaging features of liver and spleen sarcoidosis include visceromegaly, with multiple nodules hypodense on CT images and hypointense on T2-weighted MRI acquisitions. Main clinical and radiological manifestations of renal sarcoidosis are nephrolithiasis, nephrocalcinosis, and acute interstitial nephritis. Brain sarcoidosis shows multiple or solitary parenchymal nodules on MRI that enhance with a ring-like appearance after gadolinium. In spinal cord localization, MRI demonstrates enlargement and hyperintensity of spinal cord, with hypointense lesions on T2-weighted images. Skeletal involvement is mostly located in small bone, showing many lytic lesions; less frequently, bone lesions have a sclerotic appearance. Ocular involvement includes uveitis, conjunctivitis, optical nerve disease, chorioretinis. Erythema nodosum and lupus pernio represent the most common cutaneous manifestations encountered. Sarcoidosis in various organs can be very insidious for radiologists, showing different imaging features, often non-specific. Awareness of these imaging features helps radiologists to obtain the correct diagnosis. TEACHING POINTS: • Systemic sarcoidosis can exhibit abdominal, neural, skeletal, ocular, and cutaneous manifestations. • T2 signal intensity of hepatosplenic nodules may reflect the disease activity. • Heerfordt's syndrome includes facial nerve palsy, fever, parotid swelling, and uveitis. • In the vertebrae, osteolytic and/or diffuse sclerotic lesions can be found. • Erythema nodosum and lupus pernio represent the most common cutaneous manifestations.

Executive dysfunctions in migraine with and without aura: what is the role of white matter lesions?

OBJECTIVE/BACKGROUND: Executive dysfunctions and white matter lesions on magnetic resonance imaging have been reported in migraine. The aim of this study was to determine whether any correlation between these 2 variables exists. MATERIALS AND METHODS: Forty-four subjects affected by migraine with or without aura were compared with 16 healthy subjects. A battery of neuropsychological tests assessing executive functions was administered to all subjects. Number and total volume of white matter lesions were assessed in the whole brain and in the frontal lobe. RESULTS: The performances of both groups of migraineurs, with and without aura, were significantly worse when compared with controls on Boston Scanning Test. Moreover, we found lower performances compared with controls respectively on Frontal Assessment Battery in patients with migraine with aura and on Controlled Oral Word Association Test in patients with migraine without aura. Nineteen patients (43.2%) and one control subject (6.2%) had white matter lesions. We did not find any significant correlation between white matter lesions load and neuropsychological performances. CONCLUSIONS: On the basis of our results, white matter lesions load on magnetic resonance imaging do not seem to contribute to neuropsychological performances deficit in migraineurs.

Aquaporin and vascular diseases.

Aquaporins (AQP) are family of water channels found in several epithelial and endothelial cells, whose recent identification has provided insights into water transport in several tissues, including the central nervous system (CNS). Since brain edema continues to be the main cause of death from several CNS diseases, such as stroke, much of the interest in AQPs and their functional contribution to the water balance is due to their possible role in clearing edema water from the brain and in managing hydrocephalus and benign intracranial hypertension, suggesting that they could be targets for future treatments of various brain conditions, particularly vascular diseases. AQPs also seem to be involved in cell migration, and a mechanism of AQP-facilitated cell migration has been proposed where local osmotic gradients created at the tip of the lamellipodium drive water influx, facilitating lamellipodial extension and cell migration. AQP-facilitated cell migration was also detected in tumour cells, suggesting that it may have an important role in tumour angiogenesis and spread, and accounting for AQP expression in many tumour cell types and for correlations found between AQP expression and tumour stage in some tumours.

A rare cystic non-functioning neuroendocrine pancreatic tumor with an unusual presentation.

This report describes a patient with a cystic non-functioning neuroendocrine glucagon cell pancreatic tumor presenting with demyelination of the optical nerve that had initially provoked marked monolateral reduced vision and had led to a suspected diagnosis of multiple sclerosis. Cystic degeneration is uncommon in endocrine pancreatic tumors due to their abundant vascular supply. Very few cases of cystic neuroendocrine non-functioning pancreatic tumors have been reported in the international literature. The presence of atypical neurological symptoms, such as sudden visual impairment, should be taken into account in the differential diagnosis for such tumors. The prognosis is poor, because most of these tumors are malignant and diagnosed at an advanced stage. The three-year disease-free survival of our patient, however, encourages the use of aggressive surgical treatment.

The combination of cyclophosphamide plus interferon beta as rescue therapy could be used to treat relapsing-remitting multiple sclerosis patients-- twenty-four months follow-up.

The aim of the present study was to evaluate the efficacy of the combination of cyclophosphamide (CTX) and interferon beta (IFN beta) in a group of relapsing remitting (RR) multiple sclerosis (MS) patients who experienced treatment failure during IFN beta therapy. It is the general experience that immunomodulatory agents (IMA) are only partially effective in RR patients. Recent data on the efficacy of immunosuppressive therapies for these patients are encouraging. The anti-inflammatory and immunosuppressive effects of CTX have been utilized to treat selected cases of multiple sclerosis with a progressive and worsening course as rescue therapy. Thirty RR MS patients with clinically defined MS who experienced treatment failure during IFN beta therapy (2 or more relapses per year or 1.5 EDSS point worsening in one year) were enrolled in the study and treated with CTX iv pulse therapy added to IFN beta and followed up for 24 months. As primary endpoints we evaluated the yearly relapse rate. We also evaluated the percentage of patients free of relapses and of EDSS variations. We analysed the results at one year before entry (T0: IFN beta alone), 12 (T1) and 24 (T2) months after entry. Brain MRI was performed at T0, at T1 and T2. The 30 RR patients who had experienced a high number of relapses (rr =1.4) at T0 showed a significant improvement in yearly relapse rate (rr = 0.4) at T1 and a further improvement (rr = 0.17) at T2 (p < 0.001). The percentage of patients free of relapse was 70% at T2 (p < 0.0001). EDSS score changed from 2.6+/-1.23 at T0 to 2.2 +/- 1.5 at T2, showing only a trend of improvement. No significant variation of MRI lesion load and no severe adverse events were recorded during the study. These data showed that the combination of CTX plus IFN beta halted the progression of disease in active and deteriorating MS patients suggesting the necessity of RCTs to test the efficacy of this combination therapy in active RRMS patients or in patients who experienced treatment failure in response to disease modifying drugs (DMDs).

A possible spatial and temporal cluster of multiple sclerosis in the town of Linguaglossa, Sicily.

We carried out an epidemiological survey to determine prevalence and incidence of multiple sclerosis in the little town of Linguaglossa in the Province of Catania. We calculated prevalence rate as point prevalence at 1 January 2001 and incidence during 1991-2000. We studied the frequency of multiple sclerosis in the community of Linguaglossa in a population of 5,422 inhabitants in the 2001 census. The primary sources for the case ascertainment were the general practitioners of Linguaglossa, the local Italian Multiple Sclerosis Association and the neurological departments, Multiple Sclerosis Centers and private neurologists of the province of Catania. We considered as prevalent and incident cases all patients who satisfied the Poser's diagnostic criteria. We detected 11 patients with multiple sclerosis who had had the onset of disease on prevalent day (P.D.). The onset-adjusted prevalence rate was 203/100,000 (95% CI 107-352). Prevalence was higher in women (247/100,000) than in men (154/100,000). From 1991 to 2000, 10 subjects with MS had clinical onset of disease. The mean annual incidence risk was 18.2/100,000 (C. I. 95 % 5.9-42.5). Conversely in the same population prevalence on 1 January 1991 was 37/100,000 while the onset adjusted annual incidence risk during the previous decade (1981-1991) was 3.6/100,000. Prevalence and incidence rates of MS during the last decade in the little town of Linguaglossa are higher than those found in the same area during the previous ten years and also than those reported in other Sicilian and Italian surveys suggesting a possible cluster of MS.

Cognitive findings after transient global amnesia: role of prefrontal cortex.

The aim of this study is to verify, after recovery, the presence of specific patterns of cognitive dysfunctions in Transient Global Amnesia (TGA). Fourteen patients with the diagnosis of TGA were submitted to a battery of neuropsychological tests and compared to a matched control group. We found significant qualitative and quantitative differences between TGA patients and controls in the California Verbal Learning Test (CLVT) and Rey-Osterrieth Complex Figure Test. Our data support the presence of selective cognitive dysfunctions after the clinical recovery. Moreover, for Verbal Fluency, Digit Span Backward, and Number of Clusters in the CVLT short-term memory test, the relation resulted as positively related with the temporal interval from the TGA episode. Reduction of categorical learning, attention, and qualitative alterations of spatial strategy seem to postulate a planning defect due to a prefrontal impairment.

Relationship between clinical variables and cognitive performances in migraineurs with and without aura.

Conflicting data on cognitive defects in migraine could be explained by differences in the clinical variables of the populations studied. We investigated 21 patients with migraine with aura and 24 with migraine without aura, diagnosed according to the International Headache Society criteria. The patients were submitted to a comprehensive battery of neuropsychological tests and grouped according to attack frequency and side of pain. Attack frequency was not associated with significant differences in any of the tasks, while location of pain was found to be significantly related to poorer performance on both the immediate and delayed recall of Rey Complex Figure in migraineurs both with and without aura, and a significant relationship between side of pain and number of clusters in the second trial of California Verbal Learning Test was found only in migraine with aura patients. The finding of worse performances in patients with right-sided pain seems to support a right hemisphere dysfunction hypothesis.

Long lasting effects of transcranial direct current stimulation on motor imagery.

Transcranial magnetic stimulation (TMS) was employed to probe the modulatory effects of transcranial direct current stimulation of motor cortex on motor evoked responses (MEPs) produced during motor imagery. MEP amplitudes at rest and during motor imagery were assessed before and for a period of 60 min after transcranial direct current stimulation (tDCS) applied over the primary motor cortex at 1 mA for 5 min. Cathodal stimulation induced a decrease of about 30% of MEP amplitude at rest and a 50% reduction of MEP size during imagery. Ten minutes after tDCS, MEPs at rest returned to baseline values while MEPs during motor imagery were suppressed for up to 30 min. No changes in MEP amplitude during imagery were found after anodal stimulation. tDCS could represent a powerful tool to modulate the excitability of motor areas involved in mental practice and motor imagery.

Stabilization of rapidly worsening multiple sclerosis for 36 months in patients treated with interferon beta plus cyclophosphamide followed by interferon beta.

Cyclophosphamide (CTX) is an alkylating agent related to nitrogen mustards whose anti-inflammatory and immunosuppressive effects have been utilised to treat selected cases of multiple sclerosis with a progressive and worsening course. To halt the progression of disease in patients refractory to disease modifying drugs CTX has been given, and several open-label studies have recently shown clinical benefits. In a previous study we demonstrated the effectiveness of a combination of IV monthly pulses of CTX and interferon beta (IFN-beta) in 10 patients with "rapidly transitional" form of multiple sclerosis characterised by severe and frequent attacks and rapid progression of disability. The present study reports the clinical and MRI follow-up 36 months after the discontinuation of CTX showing the maintenance of the results obtained in relapse rate (p<0.001), EDSS (p<0.001), T2 MRI total lesion load (p<0.001) and T2 lesions number (p<0.001) compared to the pre-treatment period. These encouraging findings and the absence of significant recorded side effects affirm that the association of CTX plus interferon-beta is amenable, safe and can be recommended in rapidly worsening MS patients.